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BACKGROUND@#The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos.METHOD: This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs. @*RESULTS@#Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries. @*CONCLUSION@#The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.
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BACKGROUND@#Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration.METHOD: Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns. @*RESULTS@#Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like Prl and Igfbp1, pivotal in uterine decidualization. @*CONCLUSION@#Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PDL1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.
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Background@#This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. @*Methods@#All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. @*Results@#Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48–5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. @*Conclusions@#Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.
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Objective@#This study aims to evaluate the safety and feasibility of laterally extended endopelvic resection (LEER) for sarcoma in the female genital tract. @*Methods@#We prospectively recruited gynecologic cancer patients with sarcoma arising from female genital tract who underwent LEER at Seoul National University Hospital from December 2016 to March 2021. Clinicopathologic characteristics, surgical outcomes including postoperative complications and pain control, and survival outcomes of the patients were investigated. @*Results@#A total of nine patients were registered for this study. The median age was 56 years. Carcinosarcoma (n=2, 22%), leiomyosarcoma (n=2, 22%), and undifferentiated uterine sarcoma (n=2, 22%) were common histology types. Complete resection was achieved in 88.9%. The most common location of pelvic sidewall tumors was infra-iliac acetabulum (66.7%). The pathologic outcome showed a median tumor size of 9.0 cm and internal iliac vessel resection with pelvic sidewall muscle was performed in all patients. The median estimated blood loss was 1,600 mL (range, 300-22,300), and the patients were postoperatively admitted to the intensive care unit for median 1 day (range, 0-8). Complete response was observed in 44.4% (4/9) in radiologic studies after LEER, and median progression-free survival, treatment-related survival, and overall survival were 3.3, 19.6, and 98.9 months, respectively. @*Conclusion@#LEER was feasible and safe in treating recurrent sarcoma presenting pelvic sidewall invasion with acceptable survival outcomes and manageable postoperative complications.
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Objective@#We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. @*Methods@#We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. @*Results@#Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. @*Conclusion@#Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.
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Background@#The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. @*Methods@#We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. @*Results@#We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. @*Conclusion@#This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.
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Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.
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Objective@#The three major gynecologic cancers are cervical, endometrial, and ovarian cancer. This study aimed to describe the 19-year trends and survival rates in cervical, endometrial, and ovarian cancer in a Korean female population. @*Methods@#We searched the Korea Central Cancer Registry to identify patients with gynecologic cancer between 1999 and 2017. Age-standardized rates and annual percent changes were calculated. The relative survival rate (RSR) was reported by histology, age, and stage for each gynecological cancer. @*Results@#The total number of cervical, endometrial, primary peritoneal, ovarian epithelial, fallopian tube (POFT) cancer was 134,863, with the number of cases increasing every year: 6,077 in 1999 to 8,011 in 2017. The incidence of cervical cancer has decreased; however, that of POFT and endometrial cancer has increased. The 5-year RSR of cervical, POFT, and endometrial cancer was reported to be 80.8%, 61.4%, and 88.1%, respectively. In the case of cervical cancer, squamous cell carcinoma showed better survival than other histology (82.8% vs. 73.5%). Furthermore, in the case of endometrial cancer, endometrioid histology had substantially better 5-year RSR than the others (93.2% vs. 76.5%). Contrastingly, in the case of ovarian cancer, serous carcinoma had worse 5-year RSR than other types of histology. @*Conclusion@#The incidence rates for gynecologic cancers increased from 2005 to 2017, with an annual increase of 2.76 per year until 2017. Endometrial cancer had the highest RSR, while ovarian cancer had the lowest. Active cancer screening and the introduction of effective treatments might have contributed to the improved RSRs of gynecologic cancers.
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Background@#The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. @*Methods@#We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. @*Results@#We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. @*Conclusion@#This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.
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The second-line chemotherapy using paclitaxel, carboplatin, and bevacizumab for treating platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer frequently cause chemotherapy-induced peripheral neuropathy (CIPN), which is significantly associated with deterioration of quality of life. Despite the potential of some agents to prevent and treat CIPN, and there is still a lack of evidence of the effect. Although selenium has been suggested as an antioxidant candidate to prevent CIPN, there are insufficient data regarding its effect due to its low dose by oral administration. Thus, we hypothesized intravenous administration of high-dose selenium (2,000 µg/day) at each cycle of the second-line chemotherapy would prevent and reduce CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer.MethodThis trial is an investigator-initiated, phase III, double-blinded, randomized controlled trial to evaluate the efficacy and safety of intravenous administration of high-dose selenium (2,000 µg/day) for preventing CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer who receive paclitaxel, carboplatin, and bevacizumab. A total of 68 patients will be randomly assigned to the experimental and control groups at a 1:1 ratio. As the primary endpoint, the incidence rate of CIPN three months after six cycles of chemotherapy will be compared between the two groups according to the combined criteria of neuropathy using the World Health Organization-CIPN criteria and Common Terminology Criteria for Adverse Events version 5.0. As secondary endpoints, we will compare adverse events, patient-reported quality of life, and requirement of concomitant drugs for reducing CIPN between the two groups.
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Objective@#A neuropsychological battery is a gold standard for thorough cognitive evaluation. However, it could not be used as a screening test due to its long inspection time and high cost. This study is conducted to identify specific cognitive subdomains that alter even at the early stage of cognitive decline. @*Methods@#Neuropsychological battery results of 575 persons who visited memory clinic were analysed. We classified stages of cognitive decline according to Clinical Dementia Rating (CDR) and CDR-Sum of boxes (CDR-SB). To explore which subdomains can sensitively distinguish normal cognition from the early cognitive impairment, we used Variable Importance in Projection (VIP) in addition to analysis of covariance. @*Results@#We found that scores in subdomain tests such as Rey Complex Figure Test immediate and delayed recall successfully differentiate persons with CDR 0 from those with CDR 0.5 and also persons with CDR-SB 0 from those with CDR-SB 0.5 as indicated by VIP values greater than 1. @*Conclusion@#These results suggest that alterations in visuospatial memory function might be a sensitive sign reflecting the early cognitive decline. The combination of only a few subtests could be also used as a reliable and sensitive screening tool to detect early cognitive impairment.
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Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.
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Objective@#The three major gynecologic cancers are cervical, endometrial, and ovarian cancer. This study aimed to describe the 19-year trends and survival rates in cervical, endometrial, and ovarian cancer in a Korean female population. @*Methods@#We searched the Korea Central Cancer Registry to identify patients with gynecologic cancer between 1999 and 2017. Age-standardized rates and annual percent changes were calculated. The relative survival rate (RSR) was reported by histology, age, and stage for each gynecological cancer. @*Results@#The total number of cervical, endometrial, primary peritoneal, ovarian epithelial, fallopian tube (POFT) cancer was 134,863, with the number of cases increasing every year: 6,077 in 1999 to 8,011 in 2017. The incidence of cervical cancer has decreased; however, that of POFT and endometrial cancer has increased. The 5-year RSR of cervical, POFT, and endometrial cancer was reported to be 80.8%, 61.4%, and 88.1%, respectively. In the case of cervical cancer, squamous cell carcinoma showed better survival than other histology (82.8% vs. 73.5%). Furthermore, in the case of endometrial cancer, endometrioid histology had substantially better 5-year RSR than the others (93.2% vs. 76.5%). Contrastingly, in the case of ovarian cancer, serous carcinoma had worse 5-year RSR than other types of histology. @*Conclusion@#The incidence rates for gynecologic cancers increased from 2005 to 2017, with an annual increase of 2.76 per year until 2017. Endometrial cancer had the highest RSR, while ovarian cancer had the lowest. Active cancer screening and the introduction of effective treatments might have contributed to the improved RSRs of gynecologic cancers.
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OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533
Subject(s)
Humans , Alopecia , Carboplatin , Cohort Studies , Disease-Free Survival , Doxorubicin , Drug Therapy , Follow-Up Studies , Hand-Foot Syndrome , Korea , Ovarian Neoplasms , Paclitaxel , Peripheral Nervous System Diseases , Platinum , Prognosis , Recurrence , Retrospective StudiesABSTRACT
OBJECTIVE@#To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.@*METHODS@#We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).@*RESULTS@#Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.@*CONCLUSIONS@#The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533
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A previous pharmacogenomic analysis identified cromolyn, an anti-allergic drug, as an effective anti-fibrotic agent that acts on hepatocytes and stellate cells. Furthermore, cromolyn was shown to be a G protein-coupled receptor 35 (GPR35) agonist. However, it has not been studied whether anti-fibrotic effects are mediated by GPR35. Therefore, in this study, the role of GPR35 in hepatic fibrosis was investigated through the use of lodoxamide, another anti-allergic drug and a potent GPR35 agonist. Longterm treatment with carbon tetrachloride induced hepatic fibrosis, which was inhibited by treatment with lodoxamide. Furthermore, CID2745687, a specific GPR35 antagonist, reversed lodoxamide-mediated anti-fibrotic effects. In addition, lodoxamide treatment showed significant effects on the mRNA expression of collagen Iα1, collagen Iα2, and TGF-β1 in the extracellular matrix. However, a transforming growth factor α (TGF-α) shedding assay revealed lodoxamide not to be a potent agonist of mouse GPR35 in vitro. Therefore, these results showed anti-fibrotic effects of lodoxamide in mice and raise concerns how lodoxamide protects against liver fibrosis in vivo and whether GPR35 is involved in the action.
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PURPOSE: The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers. MATERIALS AND METHODS: The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management. RESULTS: Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001). CONCLUSION: RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.
Subject(s)
Female , Humans , Male , Breast , Breast Neoplasms , Korea , National Health Programs , Ovarian Neoplasms , Prophylactic Surgical ProceduresABSTRACT
Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the aging population after Alzheimer’s disease (AD). Defects in the lysosomal systems and mitochondria have been suspected to cause the pathogenesis of PD. Nevertheless, the pathogenesis of PD remains obscure. Abnormal cholesterol metabolism is linked to numerous disorders, including atherosclerosis. The brain contains the highest level of cholesterol in the body and abnormal cholesterol metabolism links also many neurodegenerative disorders such as AD, PD, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The blood brain barrier effectively prevents uptake of lipoprotein-bound cholesterol from blood circulation. Accordingly, cholesterol level in the brain is independent from that in peripheral tissues. Because cholesterol metabolism in both peripheral tissue and the brain are quite different, cholesterol metabolism associated with neurodegeneration should be examined separately from that in peripheral tissues. Here, we review and compare cholesterol metabolism in the brain and peripheral tissues. Furthermore, the relationship between alterations in cholesterol metabolism and PD pathogenesis is reviewed.
Subject(s)
Aging , Amyotrophic Lateral Sclerosis , Atherosclerosis , Blood Circulation , Blood-Brain Barrier , Brain , Cholesterol , Metabolism , Mitochondria , Neurodegenerative Diseases , Parkinson DiseaseABSTRACT
Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 (S1P₂) has not been fully investigated. Therefore, in this study, the roles of S1P₂ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the 7(th) day after bleomycin administration, S1P₂ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the 28(th) day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from S1P₂ deficient mice showed less inflammation and fibrosis. Increase in TGF-β1-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a S1P₂ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of S1P₂ were elucidated using a bleomycin-induced fibrosis model. Notably, S1P₂ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that S1P₂ could be a promising therapeutic target for the treatment of pulmonary fibrosis.
Subject(s)
Animals , Humans , Mice , Bleomycin , Bronchoalveolar Lavage , Epithelial Cells , Epithelial-Mesenchymal Transition , Extracellular Matrix , Fibrosis , Idiopathic Pulmonary Fibrosis , Inflammation , Lung , Phosphotransferases , Pneumonia , Pulmonary Fibrosis , Receptors, Lysosphingolipid , SphingosineABSTRACT
PURPOSE: The purpose of this study was to test a model of nursing competencies of nursing simulation learners. The conceptual model was based on the theory of Jeffries's simulaton theory. METHODS: Data collection was conducted in October 2017 for 310 students from two nursing universities in Kyungbuk area for 20 days. Data analysis methods were covariance structure analysis using SPSS 21.0 and AMOS 22.0 statistical programs. RESULTS: The hypothetical model was a good fit for the data. The model fit indices were comparative fit index=.97, normed fit index=.94, Tucker-Lewis Index=.97, root mean square error of approximation=.44, and standardized root mean square residual=.04. Teacher factors were directly related to simulation design characteristics, and it was confirmed that the curriculum, classroom operation and teaching method of the instructors were important factors. Learner factors were found to have a direct effect on nursing competence, self-confidence, and clinical performance that belong to nursing capacity. In particular, the results of this study indicate that the simulation design characteristics have a partial mediating effect on learner factors and clinical performance, and a complete mediating effect on learner factors and clinical judgment ability. CONCLUSION: In order to improve the learner's clinical performance and clinical judgment ability, it is necessary to conduct practical training through nursing simulation besides preparing the learner and the educator.